Is ADAT3 p.Asp55fs (c.159_160del) pathogenic?

ADAT3 p.Asp55fs (c.159160del) is classified Likely pathogenic in ADAT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-22). Very rare (popmax 0.00403%, afr); Associated with intellectual disability-strabismus syndrome.

What condition is associated with ADAT3 p.Asp55fs (c.159_160del)?

ADAT3 p.Asp55fs (c.159_160del) is associated with intellectual disability-strabismus syndrome (ClinVar).

How common is ADAT3 p.Asp55fs (c.159_160del) in the general population?

ADAT3 p.Asp55fs (c.159_160del) is very rare (popmax 0.00403%, afr) (gnomAD).

How is Intellectual disability-strabismus syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ADAT3 p.Asp55fs

c.159_160del · VCV3362604

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00403%, afr)

Conditions

intellectual disability-strabismus syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -1.1, phastCons 0.8
Overall
CADD	18.66	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00403% African / African-American · 3/74,506 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000692% 11/1,589,806 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00403%	24,835
Remaining individualsnot grpmax-eligible	0.00325%	30,813
European (non-Finnish)	0.000512%	195,251

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ADAT3
Protein: p.Asp55fs
Coding: c.159_160del
MANE Select: NM_138422
Type: Deletion
Location: chr19:1912206 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.83

Full ADAT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability-strabismus syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Intellectual disability-strabismus syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ADAT3 p.Pro10fs Likely pathogenic ★★ same condition
ADAT3 p.Ala196fs Conflicting classifications of pathogenicity ★ same condition
ADAT3 p.Asp55= Likely benign ★ same residue
ADAT3 p.Val144Met Pathogenic/Likely pathogenic ★★ same condition
ADAT3 p.Ala20Val Uncertain significance ★★ same condition
ADAT3 p.Arg250Cys Uncertain significance ★★ same condition
ADAT3 p.Gln274fs Uncertain significance ★★ same condition
ADAT3 p.Gly251Ser Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/adat3-p-asp55fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown